Anti-COVID-19 Vaccination in Patients with Autoimmune-Autoinflammatory Disorders and Primary/Secondary Immunodeficiencies: The Position of the Task Force on Behalf of the Italian Immunological Societies

The Coronavirus disease 2019 (COVID-19) pandemic has represented an unprecedented challenge for humankind from health, economic, and social viewpoints. In February 2020, Italy was the first western country to be deeply hit by the pandemic and suffered the highest case/fatality rate among western countries. Brand new anti-COVID-19 vaccines have been developed and made available in <1-year from the viral sequence publication. Patients with compromised immune systems, such as autoimmune-autoinflammatory disorders (AIAIDs), primary (PIDs) and secondary (SIDs) immunodeficiencies, have received careful attention for a long time regarding their capacity to safely respond to traditional vaccines. The Italian Immunological Societies, therefore, have promptly faced the issues of safety, immunogenicity, and efficacy/effectiveness of the innovative COVID-19 vaccines, as well as priority to vaccine access, in patients with AIADs, PIDs, and SIDs, by organizing an ad-hoc Task Force. Patients with AIADs, PIDs, and SIDs: (1) Do not present contraindications to COVID-19 vaccines if a mRNA vaccine is used and administered in a stabilized disease phase without active infection. (2) Should usually not discontinue immunosuppressive therapy, which may be modulated depending on the patient's clinical condition. (3) When eligible, should have a priority access to vaccination. In fact, immunizing these patients may have relevant social/health consequences, since these patients, if infected, may develop chronic infection, which prolongs viral spread and facilitates the emergence of viral variants

Hypophosphatemia after high-dose iron repletion with ferric carboxymaltose and ferric derisomaltose-the randomized controlled HOMe aFers study

Background In patients with iron deficiency anemia, ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) allow high-dose iron repletion. While FCM is reported to induce hypophosphatemia, the frequency of hypophosphatemia after an equivalent dosage of FDI had not been assessed prospectively. Methods In the prospective, single-center, double-blind HOMe aFers study, 26 women with iron deficiency anemia (hemoglobin < 12 g/dL plus either plasma ferritin ≤ 100 ng/mL or a plasma ferritin ≤ 300 ng/mL and transferrin saturation (TSAT) ≤ 30%) were randomized to a single intravenous infusion of 20 mg/kg body weight (up to a maximum of 1000 mg) FCM or FDI. The primary endpoint was the incidence of hypophosphatemia (plasma phosphorus levels < 2.0 mg/dL at day 1, day 7 ± 2, and/or day 35 ± 2 after the infusion). In order to investigate potential skeletal and cardiovascular implications, we assessed changes in other components of mineral and bone metabolism, left ventricular function, and arrhythmias. Results Hypophosphatemia occurred more frequently in women treated with FCM (9 out of 12 [75%]) than in those treated with FDI (1 out of 13 [8%]; p = 0.001). Within 24 h after iron supplementation, women in the FCM group had significant higher plasma intact FGF23 (p < 0.001) and lower plasma 1.25-dihydroxyvitamin D (p < 0.001). As an indicator of urinary phosphorus losses, urinary fractional phosphorus excretion was higher in the FCM group (p = 0.021 at day 7 ± 2 after iron supplementation). We did not observe differences in skeletal and cardiovascular markers, potentially because of the limited number of participants. Conclusions While both FCM and FDI provide efficient iron repletion in participants with iron deficiency anemia, FCM induced hypophosphatemia more often than FDI. Trial registration Clinical Trials.gov NCT02905539. Registered on 8 September 2016. 2015-004808-36 (EudraCT Number) U1111-1176-4563 (WHO Universal Trial Number) DRKS00010766 (Deutsches Register Klinischer Studien

Preoperative imaging findings in patients undergoing transcranial magnetic resonance imaging-guided focused ultrasound thalamotomy

The prevalence and impact of imaging findings detected during screening procedures in patients undergoing transcranial MR-guided Focused Ultrasound (tcMRgFUS) thalamotomy for functional neurological disorders has not been assessed yet. This study included 90 patients who fully completed clinical and neuroradiological screenings for tcMRgFUS in a single-center. The presence and location of preoperative imaging findings that could impact the treatment were recorded and classified in three different groups according to their relevance for the eligibility and treatment planning. Furthermore, tcMRgFUS treatments were reviewed to evaluate the number of transducer elements turned off after marking as no pass regions the depicted imaging finding. A total of 146 preoperative imaging findings in 79 (87.8%) patients were detected in the screening population, with a significant correlation with patients' age (rho = 483, p &lt; 0.001). With regard of the group classification, 119 (81.5%), 26 (17.8%) were classified as group 1 or 2, respectively. One patient had group 3 finding and was considered ineligible. No complications related to the preoperative imaging findings occurred in treated patients. Preoperative neuroradiological findings are frequent in candidates to tcMRgFUS and their identification may require the placement of additional no-pass regions to prevent harmful non-targeted heating

Tinnitus: Distinguishing between Subjectively Perceived Loudness and Tinnitus-Related Distress

OBJECTIVES: Overall success of current tinnitus therapies is low, which may be due to the heterogeneity of tinnitus patients. Therefore, subclassification of tinnitus patients is expected to improve therapeutic allocation, which, in turn, is hoped to improve therapeutic success for the individual patient. The present study aims to define factors that differentially influence subjectively perceived tinnitus loudness and tinnitus-related distress. METHODS: In a questionnaire-based cross-sectional survey, the data of 4705 individuals with tinnitus were analyzed. The self-report questionnaire contained items about subjective tinnitus loudness, type of onset, awareness and localization of the tinnitus, hearing impairment, chronic comorbidities, sleep quality, and psychometrically validated questionnaires addressing tinnitus-related distress, depressivity, anxiety, and somatic symptom severity. In a binary step-wise logistic regression model, we tested the predictive power of these variables on subjective tinnitus loudness and tinnitus-related distress. RESULTS: The present data contribute to the distinction between subjective tinnitus loudness and tinnitus-related distress. Whereas subjective loudness was associated with permanent awareness and binaural localization of the tinnitus, tinnitus-related distress was associated with depressivity, anxiety, and somatic symptom severity. CONCLUSIONS: Subjective tinnitus loudness and the potential presence of severe depressivity, anxiety, and somatic symptom severity should be assessed separately from tinnitus-related distress. If loud tinnitus is the major complaint together with mild or moderate tinnitus-related distress, therapies should focus on auditory perception. If levels of depressivity, anxiety or somatic symptom severity are severe, therapies and further diagnosis should focus on these symptoms at first

Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density.

OBJECTIVES: To identify genetic determinants of susceptibility to clinical vertebral fractures, which is an important complication of osteoporosis. METHODS: Here we conduct a genome-wide association study in 1553 postmenopausal women with clinical vertebral fractures and 4340 controls, with a two-stage replication involving 1028 cases and 3762 controls. Potentially causal variants were identified using expression quantitative trait loci (eQTL) data from transiliac bone biopsies and bioinformatic studies. RESULTS: A locus tagged by rs10190845 was identified on chromosome 2q13, which was significantly associated with clinical vertebral fracture (P=1.04×10-9) with a large effect size (OR 1.74, 95% CI 1.06 to 2.6). Bioinformatic analysis of this locus identified several potentially functional SNPs that are associated with expression of the positional candidate genes TTL (tubulin tyrosine ligase) and SLC20A1 (solute carrier family 20 member 1). Three other suggestive loci were identified on chromosomes 1p31, 11q12 and 15q11. All these loci were novel and had not previously been associated with bone mineral density or clinical fractures. CONCLUSION: We have identified a novel genetic variant that is associated with clinical vertebral fractures by mechanisms that are independent of BMD. Further studies are now in progress to validate this association and evaluate the underlying mechanism

Referendum del 12-13 giugno 2011 a Roma: la campagna e la partecipazione

Il Comune di Roma e i suoi Municipi Territorio, comunicazione e mobilitazione La campagna referendaria Municipio per Municipio La partecipazione a Roma nelle elezioni e nei referendum La partecipazione nel referendum del 12-13 giugn

Clinical and immunological response to typhoid vaccination with parenteral or oral vaccines in two groups of 30 recruits

The clinical and immunological responses to typhoid vaccination with parenteral and oral vaccines in two groups of 30 adult male subjects were studied. Specific anti-Salmonella typhi cell-mediated immunity and total or specific anti-lipopolysaccharide faecal immunoglobulin (Ig) A titres in vaccinated subjects were monitored. Cellular antibacterial activity was significantly increased only in orally vaccinated subjects. Serum arming activity and inhibition experiments suggested an IgA-dependent cellular cytotoxicity in those orally vaccinated. In these subjects, a total and antilipopolysaccharide faecal IgA increase was observed lasting up to 8 months after completion of the vaccination schedule. In parenteral vaccinated subjects, an early onset transitory increase of IgM rheumatoid factor was observed. Oral vaccine was well tolerated and free of side effects, whereas 65% of parenterally vaccinated subjects reported side effects such as fever, headache, malaise and local tenderness in the injection site